Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-kappaB signaling and T-helper cell homeostasis.

Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-kappaB signaling and T-helper cell homeostasis.

Chen Yingying; Li Rui-Yan; Shi Mei-Jing; Zhao Ya-Xing; Yan Yan; Xu Xin-Xin; Zhang Miao; Zhao Xiao-Tong; Zhang Yu-Bin

Inflammation research : official journal of the European Histamine Research Society ... [et al.]

2017

2017-02

OBJECTIVE: The activation of NF-kappaB signaling and unbalance of T-helper (Th) cells have been reported to play a key role in the pathogenesis of colitis. Cortex Phellodendri Chinensis (CPC) is commonly used to treat inflammation and diarrhea. Demethyleneberberine (DMB), a component of CPC, was reported to treat alcoholic liver disease as a novel natural mitochondria-targeted antioxidant in our previous study. In this study, we investigated whether DMB could protect against dextran sulfate sodium (DSS)-induced inflammatory colitis in mice by regulation of NF-kappaB pathway and Th cells homeostatis. METHODS: Inflammatory colitis mice were induced by 3% DSS, and DMB were orally administered on the doses of 150 and 300 mg/kg. In vitro, DMB (10, 20, 40 muM) and N-acetyl cysteine (NAC, 5 mM) were co-cultured with RAW264.7 for 2 h prior to lipopolysaccharide (LPS) stimulation, and splenocytes from the mice were cultured ex vivo for 48 h for immune response test. RESULTS: In vivo, DMB significantly alleviated the weight loss and diminished myeloperoxidase (MPO) activity, while significantly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha), and inhibited the activation of

Animals; Anti-Inflammatory Agents/*pharmacology/therapeutic use; Berberine/*analogs & derivatives/pharmacology/therapeutic use; Colitis; Colon/drug effects/immunology/pathology; Cytokines/immunology; Dextran Sulfate; DMB; Female; Helper-Inducer/*drug effects/immunology; Homeostasis/drug effects; Immunoglobulin G/blood; Inbred C57BL; Inflammatory Bowel Diseases/blood/chemically induced/drug therapy/*immunology; Mice; NF-kappa B/*antagonists & inhibitors/immunology; NF-kappaB; RAW 264.7 Cells; Reactive Oxygen Species/metabolism; Signal Transduction/drug effects; Spleen/cytology; T-Lymphocytes; Th cell

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